This project includes an HIV Cloning and Serology Core, HIV CMI Core, and continuing studies to define HIV structural and non-structural proteins which are recognized by cytotoxic T lymphocytes (CTL) in humans infected with HIV-1. Over the first project period of our NCVDG award, we have made significant contributions to our understanding of CTL responses in HIV-infected adults and children and have characterized the humoral response which is generated by live recombinant virus and particle vaccines in rabbits. During the next project period we propose the following: 1. HIV Cloning and Serology Core- will provide HIV genes isolated from patient isolates (infants and adults) obtained from the U.S. as well as Africa; determine neutralizing antibody responses in rabbits following immunization with recombinant vaccines and particles; perform safety assessments in immunodeficient mice of recombinant vaccina and particle vaccines. 2. HIV Cell-mediated Immunity Core- will determine CTL and Proliferative responses to live recombinant and particle vaccines in rabbits. 3. Study of Human CTL Responses to HIV-1 Structural and Non-structural Proteins - We will continue to characterize in vivo CTL responses in HIV- 1 infected infants and adults by looking at a variety of HIV-1 proteins and virus strains including responses against HIV-1 strains will be compared with responses to autologous viral isolates. We have established a broad clinical base which includes both pediatric and adult patients. With our experience in HIV-1 virology and immunology, we are poised to contribute to the development of HIV-1 vaccines which will prevent HIV-1 infection in adults and interrupt maternal-fetal HIV-1 transmission.